In vivo circumvention of P-glycoprotein-mediated multidrug resistance of tumor cells with SDZ PSC 833.

摘要: The new nonimmunosuppressive cyclosporin analogue, SDZ PSC 833, is a very potent multidrug-resistance modifier. In vitro , it was shown to be at least 10-fold more active than A (Sandimmune), itself verapamil, on most P -glycoprotein-expressing multidrug-resistant (MDR) tumor cell lines. vivo 833 tested in few protocols of combined therapy with either Vinca alkaloids or doxorubicin as anticancer drugs, using the homologous tumor-host system (P388 cells DBA/2 origin grafted into B6D2F1 mice). Although these MDR-P388 belong highly resistant variant that required about 150-fold drug for 50% growth inhibition parental P388 cells, significant prolongation survival times tumor-bearing mice obtained when treated combination p.o. were otherwise ineffective doses drugs given i.p. This chemosensitizing effect dose-dependent and effective protocol combining administration 4 h before injection: comparison alone, pretreatment 25 50 mg/kg gave 2- 3-fold increases times. Since used our studies variant, much higher degree resistance one known occur cancer patients, appears promising chemosensitizer.